Cardiovascular and Diabetic Medications That Cause Bradykinin-Mediated Angioedema

J Allergy Clin Immunol Pract. 2017 May-Jun;5(3):610-615. doi: 10.1016/j.jaip.2017.03.017.


Medication-induced angioedema is a bradykinin-mediated process that results from increased production or decreased degradation of bradykinin. These reactions are documented for several cardiac medications including blockers of the renin-angiotensin-aldosterone system (RAAS). Other cardiovascular and diabetes medications further increase the risk of medication-induced angioedema, particularly with concomitant use of RAAS inhibitors. Dipeptidyl peptidase IV inhibitors are a class of oral diabetic agents that affect bradykinin and substance P degradation and therefore can lead to angioedema. Neprilysin inhibitors are a separate class of cardiac medications, which includes sacubitril, and can lead to drug-induced angioedema especially when used in combination with RAAS inhibitors. This article discusses the proposed mechanisms by which these medications cause angioedema and how medication-induced angioedema differs from mast cell-mediated angioedema. It also details how to recognize medication-induced angioedema and the treatment options available.

Keywords: ACE inhibitors; ARBs (angiotensin receptor blockers); Angioedema; Bradykinin; Dipeptidyl peptidase IV inhibitors; Icatibant; Neprilysin inhibitors.

Publication types

  • Review

MeSH terms

  • Aminobutyrates
  • Angioedema / etiology*
  • Angioedema / prevention & control
  • Angiotensin Receptor Antagonists / therapeutic use*
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Animals
  • Biphenyl Compounds
  • Bradykinin / analogs & derivatives
  • Bradykinin / metabolism
  • Bradykinin B2 Receptor Antagonists / therapeutic use*
  • Diabetic Cardiomyopathies / drug therapy*
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Drug Combinations
  • Humans
  • Neprilysin / metabolism
  • Renin-Angiotensin System
  • Substance P / metabolism
  • Tetrazoles
  • Valsartan


  • Aminobutyrates
  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Biphenyl Compounds
  • Bradykinin B2 Receptor Antagonists
  • Dipeptidyl-Peptidase IV Inhibitors
  • Drug Combinations
  • Tetrazoles
  • Substance P
  • icatibant
  • Valsartan
  • Neprilysin
  • Bradykinin
  • sacubitril and valsartan sodium hydrate drug combination